Xing Jingxian, Liu Junyan, Liu Juan, Xu Zesheng
Second Department of Cardiovascular Medicine, Cangzhou Central Hospital, Cangzhou, Hebei, People's Republic of China.
Gen Physiol Biophys. 2020 Sep;39(5):461-470. doi: 10.4149/gpb_2020021.
Globally, acute myocardial infarction (AMI) is a serious condition affecting millions of individuals. While AMI therapy improves blood flow during surgery, reperfusion-induced injury may also occur, leading to secondary cardiac damage or even death. Here, we investigated miR-129-5p in myocardial ischemia-reperfusion (I/R) injury in rats, to explore reperfusion-related molecular mechanisms in myocardium. We used Sprague Dawley rats to establish a myocardial I/R model, with agomiR-129-5p injection, and used rat cardiomyocytes (H9c2) treated with anoxia-reoxygenation (A/R) to mimic myocardial I/R injury in vitro. A dual-luciferase reporter assay determined miR-129-5p binding to high mobility group box-1 (HMGB1) in H9c2 cells. We showed that exogenous miR-129-5p restored cardiac function indices, alleviated cardiac injury, relieved inflammatory effects and reduced infarct size and cell apoptosis in rat myocardium after I/R treatment. Elevated miR-129-5p induced a reduction in HMGB1 expression in rat I/R myocardium. miR-129-5p also targeted HMGB1, and negatively regulated its expression in H9c2 cells. Moreover, miR-129-5p overexpression in the cardiomyocytes reduced cell apoptosis and recovered cell viability after A/R injury, which was reversed by subsequent HMGB1 overexpression. These findings suggest miR-129-5p plays a cardioprotective role in ameliorating myocardial I/R injury in rats, by negatively targeting HMGB1. This mechanism provides new insights into the treatment of myocardium reperfusion-related damage.
在全球范围内，急性心肌梗死（AMI）是一种严重的疾病，影响着数百万人。虽然AMI治疗可在手术期间改善血流，但再灌注诱导的损伤也可能发生，导致继发性心脏损伤甚至死亡。在此，我们研究了大鼠心肌缺血再灌注（I/R）损伤中的miR-129-5p，以探索心肌中与再灌注相关的分子机制。我们使用Sprague Dawley大鼠建立心肌I/R模型，并注射agomiR-129-5p，同时使用经缺氧复氧（A/R）处理的大鼠心肌细胞（H9c2）在体外模拟心肌I/R损伤。双荧光素酶报告基因检测确定了miR-129-5p与H9c2细胞中高迁移率族蛋白B1（HMGB1）的结合。我们发现，外源性miR-129-5p可恢复I/R处理后大鼠心肌的心脏功能指标，减轻心脏损伤，缓解炎症反应，并减小梗死面积和细胞凋亡。I/R处理后的大鼠心肌中，miR-129-5p升高导致HMGB1表达降低。miR-129-5p还靶向HMGB1，并在H9c2细胞中负调控其表达。此外，心肌细胞中miR-129-5p过表达可减少A/R损伤后的细胞凋亡并恢复细胞活力，随后HMGB1过表达可逆转这一作用。这些发现表明，miR-129-5p通过负向靶向HMGB1在减轻大鼠心肌I/R损伤中发挥心脏保护作用。这一机制为心肌再灌注相关损伤的治疗提供了新的见解。
